Coronary 18F-Sodium Fluoride Uptake Predicts Outcomes in Patients With Coronary Artery Disease

Abstract

Background: Reliable methods for predicting myocardial infarction in patients with established coronary artery disease are lacking. Coronary ¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET) provides an assessment of atherosclerosis activity.

Objectives: This study assessed whether ¹⁸F-NaF PET predicts myocardial infarction and provides additional prognostic information to current methods of risk stratification.

Methods: Patients with known coronary artery disease underwent ¹⁸F-NaF PET computed tomography and were followed up for fatal or nonfatal myocardial infarction over 42 months (interquartile range: 31 to 49 months). Total coronary ¹⁸F-NaF uptake was determined by the coronary microcalcification activity (CMA).

Results: In a post hoc analysis of data collected for prospective observational studies, the authors studied 293 study participants (age: 65 ± 9 years; 84% men), of whom 203 (69%) showed increased coronary ¹⁸F-NaF activity (CMA >0). Fatal or nonfatal myocardial infarction occurred only in patients with increased coronary ¹⁸F-NaF activity (20 of 203 with a CMA >0 vs. 0 of 90 with a CMA of 0; p < 0.001). On receiver operator curve analysis, fatal or nonfatal myocardial infarction prediction was highest for ¹⁸F-NaF CMA, outperforming coronary calcium scoring, modified Duke coronary artery disease index and Reduction of Atherothrombosis for Continued Health (REACH) and Secondary Manifestations of Arterial Disease (SMART) risk scores (area under the curve: 0.76 vs. 0.54, 0.62, 0.52, and 0.54, respectively; p < 0.001 for all). Patients with CMA >1.56 had a >7-fold increase in fatal or nonfatal myocardial infarction (hazard ratio: 7.1; 95% confidence interval: 2.2 to 25.1; p = 0.003) independent of age, sex, risk factors, segment involvement and coronary calcium scores, presence of coronary stents, coronary stenosis, REACH and SMART scores, the Duke coronary artery disease index, and recent myocardial infarction.

Conclusions: In patients with established coronary artery disease, ¹⁸F-NaF PET provides powerful independent prediction of fatal or nonfatal myocardial infarction.

Keywords: (18)F-NaF PET; coronary artery disease; coronary computed tomography; coronary event risk prediction; myocardial infarction.

Figure 1.. Coronary disease activity and plaque burden in patients with and without future myocardial infarction.

Coronary microcalcification activity (CMA, top row), maximum target to background ratios (TBR, middle row) and the coronary calcium scores (CCS, bottom row) in patients with and without myocardial infarction during follow-up. For the Kaplan-Meier curves patients were dichotomized according to thresholds derived from receiver operator curves using the Youden’s index: CMA=1.56, TBR=1.28 and coronary calcium score = 1199 Agatston-units.

Figure 2.. Case examples of ¹⁸F-sodium fluoride positron emission tomography in patients with established coronary artery disease and myocardial infarction during follow-up.

Hybrid CT angiography and ¹⁸F-NaF positron emission tomography of coronary arteries in: (A) a 56-year-old male who demonstrated increased ¹⁸F-NaF uptake in the RCA at baseline and presented with an inferior ST-segment elevation myocardial infarction and occlusion of the RCA during follow-up; (B) a 52-year-old male who demonstrated increased ¹⁸F-NaF uptake in the LCx at baseline and presented with a lateral non-ST-segment elevation myocardial infarction during follow-up; (C) a 60-year-old female who showed increased ¹⁸F-NaF uptake in the proximal RCA and presented with an inferior non-ST-segment elevation myocardial infarction during follow-up. LAD–left anterior descending, LCx–left circumflex, RCA–right coronary artery.

Figure 3.. ¹⁸F-sodium fluoride positron emission tomography in the prediction of myocardial infarction in patients with established coronary artery disease.

In patients with established atherosclerosis the coronary microcalcification activity (as a marker of ¹⁸F-NaF activity across the coronary vasculature) had a significantly larger area under the receiver operator curve than the coronary calcium score (non-contrast CT), the modified Duke index (contrast CT angiography) or the REACH score (patient clinical data).AU-Agatston units, CMA–coronary microcalcification activity, REACH-Reduction of Atherothrombosis for Continued Health

Figure 4.. Predictors of myocardial infarction on Cox proportional hazards modelling.

Forest plots of hazard ratios derived from multivariable modelling with 95% confidence intervals for the coronary microcalcification activity (CMA) (A) and the target to background ratio values (B) along with covariates: coronary calcium scores, SIS, REACH score, SMART score, total number of implanted coronary stents, presence of multivessel coronary artery disease, age, gender, hyperlipidemia, hypertension, diabetes, smoking. CMA–coronary microcalcification activity, REACH-Reduction of Atherothrombosis for Continued Health, SMART - Secondary Manifestations of Arterial Disease, SIS–segment involvement score, TAG-triacylglycerides, TBR–target to background ratio

Central Illustration.. ¹⁸F-sodium fluoride positron emission tomography as a marker of disease activity in the coronary arteries is a predictor of fatal or non-fatal myocardial infarction (MI) in patients with established coronary artery disease.

¹⁸F-fluoride PET can be used to measure disease activity across the coronary vasculature and to stratify patients into those with no, low and high disease activity. Patients with high disease activity (coronary microcalcification activity (CMA) >1.56) demonstrate a >7-fold risk of myocardial infarction. These patients might therefore be suitable for advanced medical therapies including PCSK9 or interleukin 1-beta inhibition, with ¹⁸F-fluoride PET used for targeting these expensive drugs to patients at greatest risk. Patients without coronary ¹⁸F-NaF uptake (CMA=0) have an excellent prognosis with no myocardial infarctions observed during follow-up despite advanced coronary artery disease. In these patients with dormant coronary artery disease (a third of the population studied), further intensification of medical therapy might not be warranted, nor might they benefit on prognostic grounds from complex revascularization such as multivessel percutaneous intervention or coronary artery bypass grafting.